A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant

Abstract

Chlamydia trachomatis genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting genital infection and inflammation. Previously, we described a natural nanocapsule called the vault which was engineered to contain major outer membrane protein (MOMP) and was an effective vaccine which significantly reduced early infection and favored development of a cellular immune response in a mouse model. In the current study, we used another chlamydial antigen, a polymorphic membrane protein G-1 (PmpG) peptide, to track antigen-specific cells and evaluate, in depth, the vault vaccine for its protective capacity in the absence of an added adjuvant. We found PmpG-vault immunized mice significantly reduced the genital bacterial burden and histopathologic parameters of inflammation following a C. muridarum challenge. Immunization boosted antigen-specific CD4 cells with a multiple cytokine secretion pattern and reduced the number of inflammatory cells in the genital tract making the vault vaccine platform safe and effective for chlamydial genital infection. We conclude that vaccination with a Chlamydia-vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation.

A Chlamydia-Specific TCR-Transgenic Mouse Demonstrates Th1 Polyfunctionality with Enhanced Effector Function

“…Previous studies showed that a Chlamydia -specific IFNγ monofunctional Th1 clone was not protective, whereas a clone producing IFNγ and TNF cleared C. muridarum infection in nude mice (15). Vaccine models have shown that antigens and adjuvants generating polyfunctional (IFNγ+ TNF+) Th1 cells were more protective than IFNγ monofunctional Th1 cells (16, 17), and this protection has been observed in immunogenicity studies investigating single (18, 19) or multiple chlamydial antigens (20–23). …”

Advancements in prophylactic and therapeutic nanovaccines

“…Vaults are eukaryotic ribonucleoproteins assembly of a cage-like barrel-shaped structure (approximately 70 nm × 40 nm × 40 nm) made from the major vault protein (MVP) [63] . It has been shown that increased antigen-specific CD4 + T cell response with a reduction in genital bacterial load and inflammation was observed after Chlamydia muridarum polymorphic membrane protein G-1(PmpG) encapsulating vaults were administered intranasally [64] .…”

Advances and Opportunities in Nanoparticle‐ and Nanomaterial‐Based Vaccines against Bacterial Infections

“…Interestingly, the MOMP‐loaded vault nanoparticles did not stimulate TLR signaling pathways but triggered the production of IL‐1β via the activation of inflammasomes. Following intranasal immunization with vault nanocapsules loaded with either chlamydial MOMP or PmpG proteins, significant antigen‐specific antibodies and mucosal cellular responses were developed and reduced bacterial burden was observed in mice challenged with genital chlamydial infection …”

“…The self‐assembled vault protein has been exploited as a vaccine carrier to encapsulate chlamydial MOMP or antigens derived from polymorphic membrane protein G‐1 (PmpG) . The vault nanocapsules are under 100 nm in size and can be readily uptaken by dendritic cells.…”